Many types of implantable devices for repairing or improving the function of human body parts are known. Examples are vascular prostheses and grafts, tissue valves, and even completely artificial organs. The material that is used to make these implants or prostheses may be synthetic or it may be actual tissue derived from man or from some other species. For example, tissue implants often are derived from porcine or bovine sources. When an implant is made of actual tissue, the tissue may be used fresh from the donor; however, it is preferable to preserve the implant tissue for later use.
One primary obstacle to successful implantation of actual tissue implants is immune response against the implant by the recipient. Immune response against an implant is a result of antigenic differences between cells of the recipient and cells of the implant material. The recipient's natural immune response is to attack the foreign antigens on the cells of the tissue implant.
One widespread means used to overcome immune reactions against a tissue implant is to fix and preserve the tissue implant using glutaraldehyde before implantation. Theoretically, glutaraldehyde is believed to coat, bind and cross-link the antigens on the surface of the tissue implant. As a result, the number of antigens on the implant that are capable of inducing an immune response in the recipient are reduced.
Glutaraldehyde-preserved tissue implants are relatively inert biologically and have demonstrated long-term durability in some instances even though the glutaraldehyde renders them somewhat cytotoxic. However, glutaraldehyde treated implants also have demonstrated serious drawbacks, such as tissue-fatigue and a propensity toward calcification. Glutaraldehyde tends to leach out of a tissue implant into both the surrounding tissue and into the bloodstream. Also, because glutaraldehyde is cytotoxic, the cells exposed to the leached glutaraldehyde can be damaged. Cells damaged by glutaraldehyde often die and/or rupture. Dead and/or ruptured cells often serve as a nidus for calcification. In fact, calcification has proven to be one of the primary reasons for failure of glutaraldehyde-treated implants.
One solution to this calcification problem has been to fix and preserve tissue implants using photooxidation rather than glutaraldehyde. Photooxidation involves placing the tissue implant in saline, exposing the implant to a photocatalytic dye, and then subjecting the implant to fluorescent light. Photooxidation also modifies the structure of the collagen and appears to provide new cross-links in the collagenous tissue. However, implants that have been fixed using photooxidation do not exhibit the same tendency to calcify as glutaraldehyde-treated implants.
Although photooxidative fixing of tissue implants shows great promise, the implant still must be sterilized before it can be implanted in the recipient. Unfortunately, the most common method used to sterilize a tissue implant is to treat the implant with glutaraldehyde. Sterilization with glutaraldehyde, even after the tissue implant has been fixed, still could create a calcification problem. Therefore, it would be advantageous if tissue implants could be sterilized without using glutaraldehyde.
Historically, many germicidal or disinfectant solutions have been used to sterilize various objects and materials. The majority of such solutions have been used to disinfect solid surfaces. However, some disinfectant solutions have been used to disinfect soft surfaces, including human skin. Some of the disinfectant solutions previously used to sterilize human tissue, for example, the preparation known by the trademark "Betadine.TM.," have been iodine-based. Although iodine-based disinfectants have been used safely and effectively to sterilize the surface of living tissue, iodine-based solutions have not been used to sterilize non-living tissue such as the tissue found in a tissue implant.
Whether or not an iodine-based disinfectant solution can safely and effectively sterilize the non-living tissue in a tissue implant is a valid concern. Living tissue can survive relatively rigorous conditions because living tissue is capable of repairing any damage that may result from such conditions. In contrast, non-living tissue cannot repair itself. When the proteins in non-living tissue are subjected to rigorous conditions, they tend to denature. Denaturation of the protein in the tissue implant, which cannot be repaired by the non-living tissue, detrimentally affects the physical properties of the tissue implant.
A method of sterilizing tissue implants which does not cause protein denaturation and which does not induce calcification in vivo would be highly desirable.